Bioavailability of morphine in rabbits after rectal administration of suppository containing controlled release...

Two kinds of sustained release morphine suppositories have been prepared; one is an oleaginous base suppository (MSC) containing a controlled release morphine tablet (MST: MS Contin), and the other is a hollow-type suppository (MSCH) containing MST and morphine powder packed in its hollow space. In vitro release tests and in vivo rectal absorption experiments in rabbits were performed. The profiles of morphine release from MST and MSC in vitro were similar, and revealed that suppository bases had no effect on the release profile of morphine from the preparation. Morphine release from MSCH was rapid in the early phase, and then enclosed morphine was slowly and continuously released from MST. Phamacokinetics of morphine from the suppository were compared with the orally administered MST, and it was found that there was no difference in the maximum plasma concentration (Cmax) and the peak time (Tmax) between MSC and MST, but the mean residence time (MRT) of MSC was approximately three times longer than that of MST, and the extent of bioavailability (BA) of MSC was significantly larger than that of MST (71.6 +/- 14.2% and 11.9 +/- 4.0%, respectively). Cmax can be altered arbitrarily by changing the morphine content in the hollow space of MSCH. As in the case of MSC, the plasma concentration of morphine from MSCH was maintained. It is concluded from the above results that MSC is a satisfactory sustained release morphine suppository for the treatment of cancer pain, administering it twice a day, and that MSCH is effective due to its fast analgesic effect and sustained release nature not only for cancer pain but also for surgical operations.